>> I WANT TO WELCOME EVERYONE TO THE 21st MEET AND I SERVE AS THE DESIGNATED FEDERAL OFFICIAL FOR THIS WORK GROUP. WE HAVE SEVERAL NEW MEMBERS JOINING US TODAY AND WE HAVE SEVERAL WHO WILL BE ROTATING OFF AND DR. NGAI WILL GIVE A FORM INTRODUCTION AND FAREWELL TO THOSE WHO ARE LEAVING AND THE SUCCESS OF THE BRAIN INITIATIVE. AS A REMINDER FOR MOST AND INTRODUCTION FOR NEW MEMBERS, THE MULTI-COUNCIL WORKING GROUP IS NOT A FORMAL ADVISORY GROUP. I DOESN'T FALL UNDER THE FEDERAL ADVISORY COMMITTEE ACT BUT ESTABLISHED WHEN BRAIN WAS ESTABLISHED BECAUSE OF THE RECOGNIZED NEED FOR WIDE RANGING AND DIVERSE EXPERTISE IN ORDER TO BE ABLE TO PROPERLY EVALUATE THE RESEARCH BEING SUPPORTED UNDER BRAIN. EACH OF THE 10 INSTITUTES AND CENTERS HAS A REPRESENTATIVE ON THE MULTICOUNCIL WORKING GROUP MOST FROM THE RESPECTIVE ADVISORY COUNCILS BUT WE ALSO HAVE SEVERAL AT-LARGE MEMBERS TO COMPLIMENT THE EXPERTISE OF THE COUNCIL MEMBERS AND SEVERAL EX-OFFICIO MEMBERS WHO ARE PART OF NIHs FEDERAL PARTNERS INVOLVED IN THE BRAIN INITIATIVE. THE MULTICOUNCIL WORK GROUP HAS SEVERAL FUNCTIONS. THEY ONGOING OVERSIGHT OF OF THE SCIENTIFIC VISION AND PROGRESS OF THE BRAIN INITIATIVE. WE ASK FOR YOUR FEEDBACK ON CONCEPT CLEARANCES THAT ARE EXPECTED TO LEAD TO FUNDING ANNOUNCEMENTS AND IN CLOSED SESSION WE WANT YOUR INPUT ON THE FUNDING PLANS. WHEN WE TRANSITION TO CLOSED SESSION, I'LL GO OVER SOME OF THE OPERATING PROCEDURES AND IT WILL BEGIN AFTER A 45-MINUTE BREAK WHEN THE OPEN SESSION COMPLETES WHICH SHOULD BE AT AROUND 2:30. THERE'S A SEPARATE ZOOM LINK FOR THE CLOSED SESSION THAT WILL ONLY BE AVAILABLE TO MEMBERS OF COUNCIL AND GOVERNMENT EMPLOYEES. AS A REMINDER, THE OPEN SESSION IS BEING VIDEO RECORDED AND IT WILL BE POSTED ON THE NIH AND BRAIN WEBSITE. A FEW HOUSEKEEPING ITEMS, PLEASE MUTE YOUR LINE AND TURN OFF YOUR VIDEO WHEN NOT SPEAKING. THIS IS HELPFUL FOR THE VIDEOCAST. AND PLEASE TURN ON YOUR VIDEO DURING THIS DISCUSSION AND USE THE RAISED HAND OPTION IF YOU HAVE QUESTIONS AND WE'LL CALL ON YOU TO UNMUTE YOURSELF. THIS CHAT WILL NOT BE VISIBLE TO THOSE ON VIDEOCAST SO WITH THE RAISED HAND OPTION. I WANT TO THANK MY COLLEAGUES WHOSE HARD WORK GOES INTO THIS MEETING. THEY'RE WONDERFUL COLLEAGUES TO WORK WITH AS I'M SURE MOST OF YOU KNOW FROM INTERACTING WITH THEM AND UNCOMPROMISING IN THEIR DETAILS WHICH ALLOWS THIS TO RUN SMOOTHLY. WE'LL BEGIN WITH DR. JOHN NGAI AND THE CO-CHAIR OF THE WORK GROUP DR. HANK GREELY AND FINALLY WE'LL BE DISCUSSING A NEW CONCEPT THAT WILL BE PRESENTED BY DR. SHUMIN WANG. >> THANK YOU ALL FOR BEING HERE AND BIG SHOUT OUT TO YOU, SUSAN AND OTHERS FOR PUTTING THIS MEETING TOGETHER. WE'LL SEE IF IT WILL RUN SMOOTHLY WE'LL SEE IF I MANAGE TO RUN IT OFF THE RAILS IF I DO IT'S NOT THEIR FAULT AT ALL. I WANTED TO GIVE A BRIEF UPDATE ON WHAT'S GOING ON IN THE BRAIN INITIATIVE. CAN YOU SEE THE PROPER SLIDE? >> YES. >> SO JUST A BRIEF UPDATE OF THE GOINGS ON WHEN WE LAST MET IN AUGUST. WE HAVE SOME MEMBERS CYCLING OFF THIS COMMITTEE. BEFORE I JOINED BRAIN IN MAY OF 2020 FOLKS WERE APPOINTED TO THE WORKING GROUP WITH AN INDEFINITE TERM AND STARTING TO SLOWLY CYCLE PEOPLE OFF TO GIVE THEIR LIVES BACK AND THANK YOU FOR YOUR CONTRIBUTIONS. CYCLING OFF THIS ROUND IS EMMERY BROWN AND EVE MARD ARE AND JIM DESH. WE APPRECIATE ALL THEY'VE GIVEN US. WE'LL BOTH HONOR AND RESPECT YOUR CONTRIBUTIONS MOVING FORWARD WITH BRAIN TO MAKE IT ALL IT'S MINUTE TO BE. A PROFOUND DEBT OF GRATITUDE TO ALL OF YOU. WE'RE ALSO WELCOMING TODAY THREE I.C. REPS. EACH OF THE BRAIN INSTITUTE OR CENTERS HAS A REPRESENTATIVE ON THE BRAIN MULTICOUNCIL WORK GROUP. THE FIRST IS TED ABEL AT THE UNIVERSITY OF IOWA. TED WORKS ON MOLECULAR MECHANISMS OF MEMORY AND THE MOLECULAR EMPHASIS OF PSYCHOLOGICAL DISORDER AND REPRESENTING THE NATIONAL INSTITUTE OF MENTAL HEALTH ADVISORY COUNCIL. WELCOME. AND WELCOME OUR COLLEAGUE JOHN MAUNSELL THE DIRECTOR OF THE GROSSMAN INSTITUTE FOR NEUROSCIENCE. AND JOHN'S RESEARCH ARE IN ATTENTION, VISION AND USING OPTIGENETICS AND COMPUTATIONAL TECHNIQUES AND REPRESENTING THE NATIONAL INSTITUTE FOR NEUROLOGICAL DISORDERS AND STROKE. SORRY, THE CAFFEINE IS KICKING IN TOO FAST THIS MORNING. AND THE THIRD REP IS DR. TIRIN MOORE FROM STANFORD AND LOOKS AT THE NEURO MECHANISMS OF VISUAL-MOTOR INTEGRATION. HE IS HOOVER REPRESENTING THE NATIONAL EYE INSTITUTE. WITH ALSO HAVE TWO NEW MEMBERS EX-OFFICIO MEMBERS FROM NSF. WELCOME, MICHELLE. AS WELL AS KATRINA GWINN REPRESENTING OUR FEDERAL PARTNER AT THE FOOD AND DRUG ADMINISTRATION. SHE IS THE ACTING CHIEF MEDICAL OFFICER IN THE OFFICE OF CHIEF TECHNOLOGY. THESE ARE OUR NEW MEMBERS AND LOOKING FORWARD TO WORKING WITH THEM IN THE COMING YEARS. I'LL START WITH MY IMMEDIATE LEADERSHIP TEAM AND FOLKS WHO WORK WITH GREAT SCIENCE GEEKZ WHO TALK ABOUT AND IT'S WITHOUT THESE FOLKS NOTHING HERE WOULD BE POSSIBLE. THEY'RE TRYING TO KEEP SCIENCE MOVING TO HELP THEIR FOLKS IN THE EXTRAMURAL FIELD KEEP THEIR PROJECTS GOING WHILE MANY OF WHOM ARE ALSO DEALING WITH FAMILY AND OTHER ISSUES IMPOSED BY COVID. BIG BIG NOTE OF GRATITUDE TO THE PEOPLE WHO MAKE IT WORK. OUR SCIENCE IS ORGANIZED INTO SCIENTIFIC PROJECT TEAMS. I JUST WANT TO CALL OUT A CHANGE IN THE NEUROETHICS TEAM NOW CO-LED BY JAY CHURCHILL AND NINA HSU. WHILE WE DO MISS KARA AND ALL THESE CONTRIBUTED HERE, WE'RE LOOKING FORWARD TO NINA'S ONGOING CONTRIBUTIONS SHOES ALREADY DONE SO MUCH TO PUSH OUR EFFORTS IN THE NEURO ETHICS DOMAIN AND OTHER AREAS. I WANT TO TOUCH BASE IN TERMS OF OUR BUDGET. THIS IS THE BUDGET OUTLOOK STARTING IN 2014 THROUGH 2026. SO EACH ANNUAL BUDGET IS SPLIT INTO TWO PIECES. IN THE RED THIS REPRESENTS THE SO-CALLED BASE FUNDING WHICH COMES TO US AS LINE ITEMS IN THE ANNUAL ALLOCATION TO EACH OF THE 10 PARTICIPATING BRAIN I.C.s. ON YELLOW, IN AM BER ARE FUNDS FROM THE CURES ACT WHICH ENDS IN 2026. THIS IS THE ONLY THING WITH A HARD ENDING THE CURES ACT FUNDS. RIGHT HERE WE'RE IN FISCAL '22. NOTE FROM 2020 TO 2021, WE RECEIVED FROM CONGRESS A $100 MILLION INCREASE TO OUR BASE ALLOCATION. THIS BROUGHT US IN 2021 TO FUNDING LEVEL OF $560 MILLION. NOW IN THE BRAIN 2025 REPORT THE RECOMMENDATION WAS WE SHOULD AIM FOR A $500 MILLION ANNUAL BUDGET WHICH IS ABOUT WHERE WERE RIGHT NOW. OKAY. ANOTHER THING TO NOTE IS IN 2023 WE GOT THIS GIGANTIC INCREASE FROM THE CURES ACT $350 MILLION ON TOP OF THIS BASE FUNDING SO IN 2021, THE BASE FUNDING WAS $460. IF ALL GOES TO THE FUNDING LEVEL WE'D HAVE A FUNDING LEVEL NORTH OF $900 MILLION AND THERE'S A BUT. THE BUT IS RIGHT NOW WE'RE IN AN ONGOING CONTINUING RESOLUTION CAPS US AT THE BASE BUDGET FOR 2021. WE HOPE THE BUDGET ISSUE WILL BE RESOLVED SOON AND CAN GET ACCESS TO OUR FULL FUNDING LEVEL WHICH IS PROJECTED, EXPECTED TO BE AT $612 MILLION WITH THE $152 MILLION ADDITIONAL FROM THE CURES ACT FUND. STAY TUNED. THESE ARE ALL ESTIMATES RIGHT NOW LOOKING TO THE FUTURE BUT I ARGUE THE FUTURE LOOKS QUITE BRIGHT FOR BRAIN. SO A COUPLE ANNOUNCEMENTS. I WANT TO DRAW YOUR ATTENTION TO A FEW THINGS. SAVE THE DATE. THE EIGHTH ANNUAL BRAIN INITIATIVE MEETING HELD JUNE 21 THROUGH 22. THE MEETING WEBSITE AND ABSTRACT SUBMISSION SITE WILL BE OPEN VERY SOON. AND WE ARE ENCOURAGING ANYBODY WITH AN INTEREST IN WHAT BRAIN DOES OR COULD DO OR HOW IT MIGHT CONTRIBUTE TO BRAIN IS ENCOURAGED TO PARTICIPATE. THIS IS NOT JUST FOR BRAIN INITIATIVE FUNDING INVESTIGATORS AND CERTAINLY NOT JUST FOR BRAIN P.I.s. SO A COUPLE DEADLINES NOTED HERE IN LATE BREAKING NEWS WE SECURED THREE KEY NOETE SPEAKERS. WITH WILL BE MAKING A DECISION FOR WHETHER THE MEETING WILL BE HEADLINE IN A FULL VIRTUAL MOTOR HYBRID MODE COMING IN MARCH. WAY I THINK IT WILL BE A FANTASTIC MEETING. TWO WORKSHOPS I WANT TO DRAW YOUR ATTENTION TO. LAST TIME WE TALKED ABOUT THE SYNCHRONIZATION CONCEPT AND MENTIONED WE'D BE HOLDING A SERIES OF WORKSHOPS TO HAMMER OUT THE DETAILS OF WHERE WE SHOULD BE GOING. DELIGHTED TO LET YOU KNOW A DOCTOR FROM UCLA AND ANOTHER FROM PRINCETON WILL BE CO-CHAIRING THIS MEETING. THANK YOU FOR THAT EFFORT. THIS GOAL WILL BE SCIENTISTS AND ENGINEERS ACROSS MULTIPLE DOMAINS TO SEE WHAT WE CAN LEVERAGE IN TERMS OF NEW TECHNOLOGIES TO BETTER UNDERSTAND BOTH HUMAN AS WELL AS NON-HUMAN BEHAVIORS AND SYNCHRONIZE THE DATA TO COME UP WITH THE CAUSAL BASE OF BEHAVIOR. THIS IS IN EARLY MARCH. THERE'S ALSO UPCOMING A WORKSHOP TO THE BRAIN ACROSS THE LINE SPAN. THIS IS BEING ORGANIZED BY OUR COLLEAGUES AT NICHD IN COLLABORATION WITH THE BILL AND MELINDA GATES FOUNDATION. IT HAS A KEEN INTEREST IN THIS. WE HAVE REPRESENTATIVES ON THAT WORKSHOP AND PLANNING COMMITTEE AS WELL AND WE SEEK TO IDENTIFY THE STATE OF THE ART IN TOOLS TO MEASURE CHANGES IN BRAIN CELLULAR IDENTITY, CONNECTIVITY OVER THE LIFE SPAN. MARK YOUR COLORS -- CALENDARS AND WE'LL LET YOU KNOW HOW THAT GOES. WE'VE TALKED QUITE A BIT ABOUT ACHIEVING EXCELLENCE THROUGH INCLUSIVITY. WE PUBLISHED A POSITION PIECE IN NEURON LAST OCTOBER AROUND THE NEUROSCIENCE MEETING. BRAIN IS COMMITTED TO INCREASING INCLUSIVITY IN OUR WORKFORCE AND ALL WE DO WHERE THERE ARE THREE MAIN PILLARS TO THIS APPROACH. THE FIRST IS TRAINING THE N GENERATION IN SCIENTIFIC LEADERS AND HAVE AWARDS AND OUR DIFFERENCE TI FOCUSSED F99K00 AND K99R00 PATHWAY TO INDEPENDENCE AWARDS FOCUSSED ON WOMEN AND UNDER REPRESENTATIVES GROUPS. WE'RE ALSO FUNDING QUITE A FEW DIVERSITY SUPPLEMENTS TO ALLOW CURRENTLY FUNDED BRAIN INVESTIGATORS TO BRING IN TRAINEES AT VARIOUS LEVELS OF EDUCATION FROM DIVERSE BACKGROUNDS TO GET THEM INTERESTED IN WHAT WE DO IN BRAIN AND NEUROSCIENCE MORE GENERALLY AND HOPEFULLY GIVE THEM A PATH TOWARDS SECURING INDEPENDENT FUNDING AS THEY MOF ON IN THESE AREAS. WE'RE ALSO INTERESTED IN ENGAGING NEW PARTNERS AND CAPACITY BUILDING AND HAVE A U24 TO SUPPORT CAPACITY BUILDING AT MINORITY SERVING AND IDEA ELIGIBLE INSTITUTION FOR GENERATING PERFECT CISION CELL AXIS REGION IN COLLABORATION WITH TOOL DEVELOPERS AND EXPECT AND HOP THEY'LL BE INVOLVED IN THE EARLY R&D EFFORTS AS WELL. FINALLY WE'RE COMMITTED TO FOSTERING RESEARCH INCLUSIVE ENVIRONMENTS. OUR PLAN FOR ENHANCING DIVERSE PERSPECTIVES WE TALKED ABOUT BEFORE, HAVE BEEN ROLLED OUT INTO NINE-CURRENT BRAIN FOAs AND THEY'LL BE ROLLED OUT CONTINUOUSLY AS OUR NEW FOAs ARE ISSUED OR CURRENT ONES ARE RE-ISSUED. THE PDPs BEEN PICKED UP ACROSS NIH. THERE'S EIGHT RFAs TO MANY COUNCIL WITH REQUIREMENTS -- SORRY, FOR US AND MORE GENERALLY ACROSS NIH THE PDP IS PICKED UP ACROSS 10 NON-BRAIN AREAS AND MECHANISMS INCLUDING THE COMMON FUND AND VARIOUS I.C.s. THIS IS ALL WORK IN PROGRESS BUT I THINK BRAIN HAS LAID OUT A GOOD STRATEGY FOR INCREASING THE DIVERSITY AND INCLUSIVITY IN OUR WORKFORCE WITH AN EYE TOWARDS ACHIEVING SCIENTIFIC EXCELLENCE. SO WE'VE HAD INTERESTING PROJECTS WITHIN BRAIN. OUR SCHOLAR IS AN ASSISTANT PROFESSOR AT MICHIGAN STATE AND THE CHALLENGE IS TO HAVE A WAY OF HOW IDEAS, THEORIES FIELD OVER TIME AS A WAY TO PREDICT WHERE FIELDS MAY BE GOING AND THERE'S SUCH AN AVALANCHE OF INFORMATION AND DATA OUT THERE, PROBABLY NO ONE OF US COULD FULLY GRASP WHAT'S FULLY OUT THERE. MOHAMED TOOK ON THE BRAIN WORKS PROJECT WHICH IS DEVELOPED A WEB APPLICATION USING NATURAL LANGUAGE PROCESSING TO MINE THE DATA IN THIS CASE THE LITERATURE TO SEE IF WE CAN IDENTIFY EMERGING FIELD AND INTERACTIONS BETWEEN FIELDS FROM THE DATA. HERE IS WHAT WE CALL THE DIFFERENT NODE AND TOPICS AND THE CONNECTION BETWEEN THEM AND SOME SEEM QUITE INTUITIVE, OTHERS WONKY AND WE CAN SEE HOW DIFFERENT FIELDS MIGHT HAVE EMERGED. WE HOPE TO GET THIS WRITTEN UP THIS YEAR AND MAKE IT GENERALLY AVAILABLE FOR OTHERS TO HELP IN THEIR ANALYSIS OF THE LITERATURE AND HOW SCIENTIFIC FIELDS EVOLVE. STAY TUNED ON THAT. OKAY. AND BUILDING THE RESOURCE WE BUILD ON BRAINS IS IMPORTANT. OUR BRAIN INITIATIVE ALLIANCE WEBSITE STARTED A RESOURCE WHERE PEOPLE CAN SUBMIT SYNOPSISES AND TOOLS THEY'RE DEVELOPING AND PUT UP IN A RESOURCE PAGE AND THERE'S A WEB FORM AND NEWSLETTER AS WELL. IF YOU HAPPEN TO GO OVER TO THE BRAIN INITIATIVE ALLIANCE WEBSITE YOU CAN FIND TERRIFIC INFORMATION ABOUT WHAT'S AVAILABLE THERE AND WE LOOK FORWARD TO DEVELOPING THIS AS WE GO ALONG IN TIME. TOGETHER WITH OUR OTHER BRAIN INITIATIVE PARTNERS. WE HAVE SEVERAL NEW FUNDING OPPORTUNITIES ON THE STREET. I'LL GO THROUGH THESE FAIRLY QUICKLY. WE HAVE OUR U24 FOR TECHNOLOGY RESEARCH DISSEMINATION AGAIN DISSEMINATION AND THAT BEING KEY AND A NEW NOTICE FOR TRANSLATIONAL DEVICE. WE'RE PARTNERING WITH THE BLUE TOOTH MED TECH PROGRAM TO ASSIST EARLY STAGE DEVELOPMENT OF BOTH INVASIVE AND NON-INVASIVE TECHNOLOGIES FOR INTERVENING AND MODULATION IN HUMANS. MUCH OF THE CHALLENGES PEOPLE HAVE IN DEVELOPING NEW TECHNOLOGIES IS GETTING THROUGH EARLY REGULATORY HURDLES AS WELL AS OTHER TECHNOLOGY DEVELOPMENT HURDLES AND THE BLUEPRINT MED TECH PRAC IS DESIGNED TO ASSIST INVESTIGATORS THROUGH THE EARLY STAGES. VERY MUCH LOOKING FORWARD TO SEEING HOW TO PARTNER WITH BLUEPRINT IN FACILITATING SOME STUDIES. THIS IS SOMETHING WE'LL BE MAKING DECISIONS ON LATER THIS SPRING AND HAVE A ROLLING SUBMISSION PROCESS THROUGH APRIL OF THIS YEAR. FINALLY, I'LL TOUCH ON THIS A BIT LATER IS OUR UPCOMING FOAs TO SPORT THE BRAIN INITIATIVE CONNECTIVITY ACROSS SCALES OR BRAIN CONNECTS PROJECTS. THESE RFAs WILL BE ISSUED IN THE SPRING WITH DUE DATES LATER THIS SUMMER. OKAY. I PUBLISHED A COMMENTARY WITH AN OVERVIEW OF THE SO-CALLED BRAIN 2.0 TRANSFORMATIVE PROJECTS. THESE ARE PROJECTS THAT WERE CONCEIVED WITH THE URGING AND IN COURAGEMENT OF THE BRAIN 2.0 TO FIND AN STAND UP LARGE PROJECTS THAT COULD POTENTIALLY TRANSFORM THE WAY WE CONDUCT RESEARCH AND APPLY IT TO THE TREATMENT OF HUMAN BRAIN AND FOCUSSING ON HUMANS. THE WHOLE BRAIN MICROCONNECTIST PROJECT AND THE PROJECT TO DEVELOP TOOLS FOR PRECISION ACCESS. IF YOU READ THROUGH THE COMMENTARY THE POINT I HOPE WE MADE WAS A, THE IMPACT THE PROJECTS MAY HAVE ON NEUROSCIENCE RESEARCH AND THE WAY THESE PROJECTS MUTUALLY SUPPORT EACH OTHER FOR PROJECTS TO REVOLUTIONIZE THE STUDY OF THE ANNIVERSARY SYSTEM IN PARTICULAR. I SHOWED SOME INVESTIGATION OF THIS SLIDE IN THE LAST COUPLE MEETING. I'LL GIVE A QUICK EVERY VIEW AND GET TO WHERE WE ARE WITH SOME BRIEF UPDATES. THE BRAIN INITIATIVE CELL ATLAS NETWORK AND WE RECEIVE THE APPLICATION FOR THIS PROJECT. THEY'RE BEING REVIEWED THIS SPRING. WE'LL BE COMING BACK TO YOU LATER THIS YEAR. THE FIRST ROUND HAS BEEN FUNDED AND THERE'S A CAPACITY RFA FOR WHAT WE ALREADY RECEIVED THE FIRST ROUND AND THE CONNECTIVITY ANALYSIS AND WE'RE EXCITED ABOUT THE FOAs. THESE ARE THE THREE PROJECTS IN FISCAL YEAR AP 21 OF WHAT WE RECEIVED IN THE BASE FUNDING $60 MILLION WERE SO-CALLED CONGRESSIONALLY DIRECTED FUNDS TO ACCELERATE THE PROJECTS. THESE WERE DIRECTED TOWARDS THE CELL ATLAS PROJECT AND ARMAMENTARIAN PROJECT AND LAST YEAR WE FUNDED APPROXIMATELY $40 MILLION ACROSS 10 AWARDS. TWO PROJECTS THAT WERE FOCUSSED ON DEVELOPING SCALABLE TOOLS FOR STUDYING BIG BRAINS. THESE WERE FROM ONGOING RFAs WE HAD BEFORE AND I THINK THIS WILL HELP US GET A HEAD START ON DEVELOPING A WHOLE HUMAN BRAIN CELL ATLAS AND THEN WE APPLIED $16 MILLION OF THESE FUNDS TO OUR PROJECTS IN THE AREA OF PRECISION CELL ATLAS ACCESS, THREE OF THE FOUR OF THESE WERE ACTUALLY FROM THE RFA I JUST DESCRIBED AND WE'RE EXCITE EXCITED ABOUT WHERE THE PROJECTS ARE GOING. MANY THANKS TO OUR FRIENDS ON THE HILL FOR GIVING US THE EXTRA FUNDS TO GOT THE PROJECTS STARTED SOONER RATHER THAN LATER. I WANT TO GIVE YOU TWO HIGHLIGHTS WITH REGARDS TO THE PROJECTS AND END WITH A BRIEF UPDATE ON WHERE WE ARE WITH THE CONNECTIVITY PROJECT. SO LAST FALL WAS A GOOD ONE FOR US. THE BRAIN INITIATIVE CELL CENSUS NETWORK PUBLISHED ED ED A TRANCHE OF 17 ARTICLES AND 10 ARTICLES IN SISTER JOURNALS AND THEY SET THIS STAGE FOR THE COLLABORATION THAT WILL BE NECESSARY TO STAND UP A WHOLE HUMAN BRAIN CELL ATLAS. I'VE SHOWN MANY OF THIS TO YOU BEFORE BUT I'LL REPEAT AGAIN BRIEFLY, WHAT WE'VE DONE HERE IS CREATED A MULTI-MODAL ANALYSIS THAT INTEGRATE THE CHARACTERISTICS ACROSS MULTIPLE MODALITIES INCLUDING MOLECULAR, INFORMATION, SPATIAL DISTRIBUTION, MORPHOLOGY, PHYSIOLOGY AND CONNECTIVITY AND AN EFFORT AND HELPED IDENTIFY PRINCIPLES OF DIVERSIFICATION OF BRAIN CELL TYPE AND SEE DIFFERENCES AND SETS THE STAGE FOR THE BRAIN CELL AND IN TERMS OF ORGANIZATION IT SHOWS IN THE RIGHT PLACE AND THE RIGHT TIME, THE POWER OF TEAM SCIENCE THERE WERE OVER 250 RESEARCHERS ON THIS PROJECT FROM OVER 45 INSTITUTIONS AND THREE CONTINENTS. THIS IS A FIRST FOR NEUROSCIENCE RESEARCH. IT WAS A GREAT TEAM TO WORK WITH. I HAD THE PRIVILEGE OF BEING A P.I. ON THE PROJECT ON MY FORM ARE LIFE AND LOOKING FORWARD TO SEE WHAT THE NEW GROUP CAN DO MOVING FORWARD ON THE PROJECT. IN TERMS OF GAINING PRECISION ACCESS TO CELL TYPES, THERE'S BEEN A LOT OF PROGRESS GOING ON IN SEVERAL DIFFERENT FIELD. IN PARTICULAR IN THE ENGINEERING OF ADENO VIRUSES AND HERE'S DAT FROM A RECENT PAPER FROM KAL -- CAL TECH AND THEY USED DISTRICTED EVOLUTION TO IDENTIFY CAPSID MUTANT OR VARIANTS WITH VARIOUS PROPISMS FOR THE BRAIN AND A -- TROPISMS AVOIDING THE LIVER AND FOUND MULTIPLE CELL TYPES IN THE BRAIN AND IMPORTANTLY AVOIDING THE LIVER YOU CAN SEE THIS HERE THIS AVOIDANCE TO THE LIVER HERE AND IMPORTANTLY THE WORK IS NOT ONLY IN MICE BUT MARMOSETS AND WE'RE GETTING CLOSE TO REGIONS THAT ONE DAY COULD BE KEY FOR DRIVING GENE THERAPY APPROACHES IN THE HUMAN BRAIN. SO STAY TUNED. I THINK THIS IS A VERY EXCITING AREA AND OTHERS WORKING IN THIS AREA ARE WORKING TOWARDS SIMILAR GOALS AS WELL. LET ME CLOSE WITH A BRIEF SUMMARY OF THE BRAIN CONNECTIVITY PROJECT. BASED ON THE WORKSHOP WE HELD LAST YEAR IT WAS PRETTY CLEAR THE TASK WILL BE DAUNTING. I THINK THE UPSHOT WAS IT COULD BE FEASIBLE OR SHOULD BE FEASIBLE TO DO IN A MOUSE BRAIN AND PROBABLY FEASIBLE TO DO AT THE AX ON LEVEL IN A HUMAN BRAIN AND WE DON'T YET HAVE THE TECHNOLOGY TO DO THAT IN A TIMELY WAY. WE DECIDED TO SPLIT THIS EFFORT INTO TWO PHASES OVER THE NEXT 10 YEARS AND THE GOALS FOR PHASE 1, THE FIRST FIVE YEARS IS TO ASSESS AND DEVELOP DIFFERENT APPROACHES THAT COULD WORK IF WE WERE TO SCALE THEM UP. AND ALONG THE WAY TO LEARN BIOLOGY ABOUT THAT. IN OTHER WORDS, WHAT WE'LL BE EXPECTING OF FOLKS THAT WE FUND IS TO DEVELOP NEW TECHNIQUES BUT TO HAVE SOME GOOD USE CASES SO WE CAN LEARN SOMETHING ABOUT RELEVANT NEURO CIRCUITS WHILE WE DEVELOP THE TECHNOLOGIES. AND THEN WE'LL EVALUATE STRATEGIC CHOICES FOR WHICH TECHNOLOGIES TO STAND UP IF ALL GOES WELL TO DEVELOP A PLAN FOR IMPLEMENTATION FOR THE SCALE UP PHASE WHICH IS PHASE 2. WE'RE ANTICIPATING A MIX OF DIFFERENT KINDS OF FUNDING OPPORTUNITY ANNOUNCEMENTS AND THEY'RE SUMMARIZED HERE. WE'LL STAND UP COMPREHENSIVE CENTERS THAT WILL BE AIMED AT CAPACITY BUILDING, TECHNOLOGY AND DEVELOPMENT AND DEMONSTRATION, DATA INTEGRATION, NEW KNOWLEDGE, IN OTHER WORDS, WE WANT TO LEARN TECHNIQUES AND THESE WILL BE FOCUSSED IN THE BIG BRAINS OR MOUSE BRAINS AT DIFFERENT LEVELS OF RESOLUTION. WE ALSO EXPECT TO FUND SMALLER PROJECTS AIMED AT DEVELOPING PERHAPS LESS WELL DEVELOPED TECHNOLOGIES THAT COULD ENHANCE THE EFFORT OVERALL AND BE INCORPORATED AND LOOKING AT LESS DEVELOPMENT AND POTENTIALLY RISK RISKIER TECHNIQUES WITH AN UPSTATE AND AN EFFORT FOR DATA COORDINATION AND EXPECT AN INTEGRATION ACROSS ALL THE GROUPS. WE WERE USING THE BICCN AS A MODEL FOR HOW TO SET UP AND COORDINATE EFFORTS ACROSS THE BOARD IN WHAT I EXPECT TO BE A HIGHLY COLLABORATIVE EFFORT TO ATTACK THIS VERY SIGNIFICANT AND DEEP PROBLEM. SO WITH THAT -- I DON'T KNOW IF WE HAVE TIME FOR QUESTIONS, SUSAN. I'LL STOP HERE. >> WE HAVE FOUR MINUTES AND WE CAN ALWAYS GO OVER BECAUSE WE HAVE A LONG BREAK IN BETWEEN OPEN AND CLOSED. ANY >> YOU HIGHLIGHT THE IMAGE ON THE BRAIN INVESTIGATORS' EFFORTS IN PUTTING THIS DIAGRAM TOGETHER. HAS HE BEEN ABLE TO USE THIS FOR NEUROSCIENCE IN GENERAL AND SCREENING GENERAL NEUROSCIENCE AND NEURONAL AND ALL THAT? IS IT DIFFERENT FOR THE BRAIN INVESTIGATOR? >> GREAT QUESTION. I BELIEVE MOHAMMAD PULLED INTO HIS DATABASE OVER 100 MILLION FROM PUB MED. ONE CAN LOOK AT THE LITERATURE AND LOOK TO SEE HOW FIELDS DEVELOP AND WHERE THE EDGES DEVELOP. YOU CAN SAY TO YOURSELF, WE DID IT AS KIND OF A TEST AND LOOK AT CERTAIN FIELD AND CERTAIN DISCOVERIES SPARK A NEW AREA OF INVESTIGATION AND YOU CAN SEE THO THOSE NODES AND EDGES DEVELOP OVER TIME AND WE THINK THIS IS A GREAT TOOL FOR LOOKING AT HOW RESEARCH AREAS HAVE DEVELOPED ACROSS THE BIOMEDICAL LITERATURE. NOW, THE ORIGINAL GOAL -- AND I THINK IT'S STILL AN ASPIRATIONAL GOAL, COULD WE BUILD A TOOL THAT WOULD ALLOW US TO PREDICT WHERE FIELDS ARE GOING. CAN WE USE THIS COMPUTER INTELLIGENCE TO HELP US THERE? SO FAR NOT WHY THE BUT WE SAW IT WAS A GOOD IDEA TO LOOK RETROSPECTIVELY FOR HOW FIELDS DEVELOPED AND PER YOUR LAST QUESTION, ONE THING WE'D LIKE TO KNOW IS WHETHER AND HOW BRAIN IS MAKING A DIFFERENCE BETWEEN THE OTHER 95% OF NIH-FUNDED NEUROSCIENCE RESEARCH SO WE CAN ASK CERTAIN QUESTIONS. ARE WE SEEING GREATER CONNECTS BETWEEN FIELD LOOKING AT BRAIN-FUNDED RESEARCH VERSUS OTHER. THAT'S A VERY QUICK EXAMPLE. THESE ARE THE KINDS OF THINGS WE WANT TO LOOK AT TO ASSESS WHAT OUR IMPACT IS TO MAKE ADJUSTMENTS TO PUSH HARDER IN AREAS THAT ARE WORKING AND AREAS THAT MAY BE LACKING. >> THANK YOU, JOHN. LOOK FORWARD TO SEEING IT. >> TED. >> HI. I'M JUST JOINING THE GROUP. THANKS. I HAVE -- FIRSTLY, I WANT TO SAY, JOHN, THANK YOU AND THIS GROUP AND SUSAN FOR PUSHING THE ENVELOPE FOR ALL OF US. IN OUR RESEARCH AREAS. THE REQUIREMENTS IN TERMS OF DIVERSITY AND THE EXPANSION YOU ALL HAVE DRIVEN HAS IMPACTED EVERYONE AT NIH AND ACROSS ALL INSTITUTIONS AND IT'S BEEN GREAT TO SEE HOW NIMBLE YOU CAN BE AND HAVING A GREAT IMPACT. I'VE BEEN STRUCK BY SOME OF MY COLLEAGUES WORKING ON CONNECTIONS TO METABOLISM -- EVEN CONNECTIONS TO CANCER OF NEURAL CONNECTIONS TO CANCER. STRUCK BY THE WORKSHOP AND REVIEW PAPER ON THE NEUROSCIENCE OF INTEROCEPTION. WE TALKED ABOUT THIS BUT THE NERVOUS SYSTEM IS MORE THAN THE BRAIN AND I THINK SOME OF THE PERIPHERAL AREAS CAN IMPACT THE WELL BEING OF SOME PATIENTS AND MAY EVEN BE THERAPEUTIC WITH SOME CANCERS. WHAT IS HAPPENING WITH THE PERIPHERAL SYSTEM AND SEEMS LIKE THERE'S IMPACT WE CAN MAKE IN THE PERIPHERY SO I WONDER ABOUT THAT. >> CLEARLY THE CENTRAL INFORMATION SYSTEM IS INTERACTING AND THERE'S QUITE A BIT GOING ON IN THE GUT-BRAIN AXIS AS WELL. SO WE ARE VERY KEEN TO EXPLORE THESE CONNECTIONS BOTH FIGURATIVELY AND LITERALLY SPEAKING. I THINK WHAT WE CAN DO IS COME AT IT FROM A CNS PERSPECTIVE AND MEET THE OTHER STUDIES SOMEWHERE ALONG THE WAY. SO WE DO HAVE PROGRAMS FOR EXAMPLE THE SPARK PROGRAM FOCUSSED ON THE PERIPHERAL SYSTEM AND THE NCCIH THE INTERO INFORMATION SYSTEM AND WE CAN FIND A WAY TO PARTNER AND PROMOTE COLLABORATIONS AND PROJECT LOOK AT THE NERVOUS SYSTEM MORE HOLISTICALLY BUT FROM DIFFERENT PERSPECTIVES. LOOK, THE MOTOR NEURON THE REASON TO EXIST IS TO MOVE MUSCLES AND TO SAY WE'RE NOT INTERESTED IN MUSCLES IS A LITTLE BIT SILLY TO MAXIMIZE THE POSSIBILITIES. >> THANKS, JOHN. >> MAYBE WE CAN MOVE ON TO HANK ON UPDATES AND ANYTHING ELSE YOU WANT TO INFORM US ABOUT. >> WELCOME TO THE NEW MEMBERS OF NEWG AND RETURNING MEMBERS. I THINK YOU'LL HEAR SOMETHING YOU HEARD BEFORE. SOME BACKGROUND ON THE NEUROETHICS WORKING GROUP FONDLY KNOWN AS THE NEWG FOR THE NEW MEMBERS. THE NEWG GOES BACK IN ONE FORM OR ANOTHER TO 2016. IT STARTED AFTER THE BRAIN INITIATIVE. WE HAVE ABOUT 10 MEMBERS, NEUROSCIENTISTS AND A COLLECTION OF PEOPLE I SAY ABOUT 10 BECAUSE JOHN IS IMPLEMENTING TERMS AND TERM LIMITS. PEOPLE ARE ROTATING ON AND OFF AND I DON'T KNOW THE EXACT COUNT TODAY. FOUR ARE MEMBERS OF THE MCWG AND ARE HERE TODAY AND WEARING TWO HATS. I WANT TO MENTION DR. TARA RAMOS WHO WAS THERE FROM THE BEGINNING AND COMMITMENT AND DEEP INTEREST IN NEURO ETHICS AND LEFT US NOT BECAUSE SHE WAS ROTATED OFF BUT TO TAKE A NEW POSITION WITH THE DATA FOUNDATION PURSUING INTEREST IN NEURO ETHICS AND WAS CRUCIAL TO THE FORMATION OF THE NEWG. WE GENERALLY MEET TWICE A YEAR. USUALLY THE DAY BEFORE THE MCWG MEETINGS IN JANUARY AND AUGUST AND WE PROVIDE INPUT BUT NEVER ADVICE TO THE BRAIN INITIATIVE SOMETIMES THROUGH THE MEETINGS AND SOMETIMES THROUGH THE MEETINGS AND PAY PLAN AND THE CON -- CONCEPTS AND PORTFOLIO ANALYSIS OF THE ENTIRE APPROXIMATE LOOKING FOR GRANTS THAT MAY HAVE NEUROETHICS ISSUES. WE PUBLISHED AT LEAST FOUR PUBLICATIONS HAVE COME OUT BASED ON NEWG ACTIVITIES. WE HELD SOME WORKSHOPS IN THE PAST. WE HAVE TWO PLANNED FOR LATER THIS YEAR. ONE ON POST-TRIAL RESPONSIBILITIES WHICH HAS BEEN A MAJOR ISSUE OF DISCUSSION THROUGHOUT THE HISTORY OF THE NEWG AND THE OTHER ON DATA SHARING WHICH HAS ALSO BEEN MAJOR WITH THE CHANGES IN THE NIH DATA SHARING POLICIES IS BECOMING EVEN MORE IMPORTANT. SO WE'LL BE DOING THOSE LATER THIS YEAR AND IT'S NOT CERTAIN BUT IT IS MY EXPECT THERE'LL PROBABLY BE PUBLICATIONS COMING OUT OF THAT. YESTERDAY'S MEETING WAS OF COURSE BY ZOOM. THE MAIN PART OF IT WAS A DISCUSSION OF ETHICAL CHALLENGES AND IMPLANTED NEURAL DEVICE RESEARCH WITH HUMAN PARTICIPANTS. THIS IS MODERATE MY CO-CHAIR FROM NIH AND FEATURED A COUPLE PRESENTATIONS. ONE FROM ASHLEY FINESINGER FROM UCLA AND ONE FROM THE UNIVERSITY OF WASHINGTON. ASHLEY'S WAS A PRESENTATION AND DISCUSSION AND PAPER CALLED INVESTIGATOR PERSPECTIVES ON ETHICAL COMMITMENTS, PRINCIPLES AND PRACTICES GUIDING INTRACRANIAL RESEARCH IN HUMANS. LONG TITLE. IT'S NOW I THINK OUT OF EMBARGO AND PUBLISHED IN NEURON AND HAD A NICE GENESIS. THE BRAIN INITIATIVE P.I.s WORKING IN THAT AREA GOT TOGETHER AS A RESEARCH ON HUMANS GROUP AND DECIDED TO START TALKING ABOUT THE ISSUES THEMSELVES. THERE WERE SOME INTERACTION WITH THE NEWG AND THIS PAPER CAME OUT AND PUT S OUT WHAT INVESTIGATORS SEE AS THE ETHICAL ISSUES WHICH WAS A REALLY INTERESTED MODEL GROUND UP FROM THE INVESTIGATORS COMING FORWARD DISCUSSION OF ETHICS AND I THINK THE NEWG WILL PROBABLY BE INTERESTED IN THINKING MORE ABOUT AS A WAY OF GOING FORWARD IN THE FUTURE. SARAH GERRING WORKED WITH IMPLANTS TALKING ETHICAL CONSIDERATIONS FOR ETHICAL CONSIDERATIONS FOR LONG-TERM STUDIES AND LEADING TO A DISCUSSION WITH ASHLEY AND SARAH AND WITH JAMES JOHNSON WHO IS A BCI BRAIN-COMPUTER INTERFACE RESEARCH PARTICIPANT. WAS A STUNNINGLY POWERFUL PARTICIPANT IN THE PANEL AS SOMEONE WHO HAS THE IMPLANT AND LIVING THROUGH THE RESEARCH. AND COMING OUT OF THAT, ONE OF THE THINGS WE NOW HAVE TO DO IS THE NEWG LEADERSHIP HAS TO FIGURE OUT WHERE TO GO FROM HERE BUT THINK THE ISSUES OF LONG-TERM HIGHLY INTERACTIVE STUDIES, INVASIVE STUDIES, FIGURING OUT EXACTLY WHAT THE UNIVERSE OF RELEVANT ISSUE STUDIES IS A BIT OF A TRICKY QUESTION BUT WE THINK THERE'S MORE ETHICAL DISCUSSIONS TO BE HAD AND MORE POTENTIALLY GUIDANCE OR INSIGHTS TO BE SHARED. THEN WE TALKED ABOUT IN A PART MODERATE ME WE TALKED ABOUT THE NEWG'S PAST, PRESENT AND FUTURE AND WHERE WE MIGHT BE HEADED. SO THAT IN APPROXIMATELY SIX MINUTES IS THE NEWG AND I'M GLAD TO SEE SUSAN SMILE AT ME KEEPING US ON TIME AND I'M HAPPY TO TRY TO ANSWER ANY OF YOUR QUESTIONS. I'M ALSO HAPPY TO ANSWER NO QUESTION. I'M REALLY GOOD AT ANSWERING NO QUESTIONS. >> ANY QUESTIONS? >> IN THE ABSENCE OF QUESTIONS I'LL SAY ONE MORE THING. PARTICIPATING IN THE NEWG HAS AT LEAST FOR ME AND I THINK ALL MY FELLOW MEMBERS, BEEN A REALLY FASCINATING OPPORTUNITY TO LOOK AT THE TRULY INTERESTING ETHICS ISSUES RAISED BY NEUROSCIENCE AND I THINK I DON'T HAVE TO TELL NEUROSCIENTISTS AND WHAT HUGE ETHICAL ISSUES IT RAISES. I'M REALLY PLEASED THE BRAIN INITIATIVE HAS TAKEN THE NEUROETHICS ISSUES SERIOUSLY AND I KNOW JOHN AND I HAD REGULAR LENGTHY DISCUSSIONS SOMETIMES WE STICK STRICTLY TO BUSINESS AND SOMETIME WE GO OFF ON BROADER QUESTIONS OF NEUROETHICS. I APPLAUD THE BRAIN INITIATIVE AND NCWG FOR TAKING THESE SERIOUSLY AND THEY'RE INFINITELY FASCINATING TO GET A CHANCE TO PLAY WITH AND I SEE A HAND. I WAS GOING POSE YOU ASK A QUESTION TO THE GROUP WHICH ASKED YESTERDAY WHICH IS NAMELY TO GET INPUT ON WHERE YOU THINK THE ISSUES NEWG SHOULD BE DEALING WITH WE SHOULD BE THINK AND HELPING NEWG PLAN. WE HAVE THE REPORT FROM THE ADVISORY COMMITTEE TO THE DIRECTOR ON NEUROETHICS AND BRAIN. THAT'S A GUIDANCE THAT'S OUT THERE PIPPEN -- THERE. I ENCOURAGE YOU TO TAKE A LOOK AT AND GET INPUT TO PRIORITIZE WHAT THE NEWG SHOULD BE TALKING ABOUT. >> IF I CAN ADD TO THAT, SILLY FOR THE NEW MEMBERS JOINING US HERE BUT ALSO AS A REMINDER FOR ALL OF US WHO HAVE WORKED ON THIS OVER THE LAST YEAR. A LOT OF WHAT WE GOT DONE IN BRAIN WE SAW THE ROLLOUT OF THE PLAN FOR ENHANCED PERSPECTIVES AND SAW THE ROLLOUT OF THE BRAIN INITIATIVE CELL ATLAS NETWORK AND FOR BOTH OF THESE LARGE EFFORTS, WE HAD TO DIG DOWN DEEP AND THINK LONG AND HARD ABOUT WHO IS DOING THE EXPERIMENTING AND WHO IS DOING THE DECIDING AND THEREFORE WHO IS GOING TO BE BENEFIT FROM THE RICHES THAT WE INTEND TO CREATE HERE. AND THESE REALLY CAME OUT OF DISCUSSIONS NOT JUST AT MCWG AND NEWG BUT JOINT DISCUSSIONS. I REALLY THINK IT SPEAKS TO THE POWER OF COLLABORATION OF BRINGING DIVERSE PERSPECTIVES TO BEAR ON EXAMINING AND THEN FINDING A WAY TO ADDRESS KEY ISSUES OF OUR TIME. CLEARLY WE HAVE A WORKFORCE AND DIVERSITY ISSUE AND I THINK BRAIN IS LEADING A WAY TO A BETTER PLACE ON THIS. IN TERMS OF THE CELL CENSUS PROJECT WE THOUGHT WHO IS IT WE NEED TO STUDY TO GET THE BEST INFORMATION OUT IN ORDER TO A, UNDERSTOOD HOW THE HUMAN BRAIN IS PUT TOGETHER AND TREAT AS MANY PEOPLE AS POSSIBLE AND HAD WE NOT HAD AN INTENSE DISCUSSION ABOUT EQUITY AND INCLUSION, I'M NOT SURE WE WOULD HAVE COME TO THIS PLACE WE CAME TO. ALL LOOKING FORWARD TO A WORK IN PROGRESS BUT SPEAKS TO THE INCREDIBLE POWER OF POWER OF COLLABORATION AND LAST YEAR WE HAD A JOINT SESSION BETWEEN THE TWO GROUPS AND NOT TO OVER BURDEN EVERYONE HERE BUT AS WALTER ASKED, WE'D LIKE YOUR INPUT ON AREAS YOU FEEL WE SHOULD BE PAYING ATTENTION TO BEYOND THE SPECIFIC EXPERIMENTS THAT WE'RE FUNDING. >> THIS YEAR MARKS, I THINK, MANY PEOPLE IN THE FIELD THINK THE 20th ANNIVERSARY FROM A NEURO ETHICS MEETING AND HASN'T BEEN JUST A TOY FOR PHILOSOPHERS AND LAWYERS AND IT'S HAD BUY IN AND PARTICIPATION FROM NEURO SCIENTISTS AND CLINICIANS AND WE SEE IT ON THE CURRENT NEWG AND EVER IN THE MCWG IS ALMOST BY DEFINITION QUALIFIED TO OFFER USING THOUGHTS, NOT ADVICE, BUT USEFUL THOUGHTS AND INPUTS ON THE NEURO ETHICS ISSUES AND IT'S CRUCIAL TO GO FORWARD THERE BE A CONTINUING DIALOGUE BETWEEN THE SCIENTISTS, CLINICIANS AND ETHICS PEOPLE AND PARTICIPANTS ALL GOING TO STRONGLY SECONDING WALTER'S SUGGESTION AND WOULD LOVE TO HEAR THOUGHTS ON WHAT THE NEWG SHOULD BE DOING. SUSAN, I THINK THERE'S 30 SECONDS LEFT. >> WE HAVE A BREAK SCHEDULED NOW BEFORE THE CONCEPT TO FEEL FREE TO CONTINUE TO THINK ABOUT THIS AND PROVIDE INPUT TO JOHN AND TO HANK AND I THINK THERE'LL BE OPPORTUNITIES TO HEAR YOU FROM AND WE THINK WE WILL. OKAY, THEN, I WILL -- NOT SEEING HANDS I'LL CALL THE BREAK AND WE'LL BE BACK AT 1:00 FOR THE CONCEPT PRESENTATION BY DR. SHUM SHUMIN WANG ON NON-INVASIST BRAIN FUNCTIONING IMAGING TECHNOLOGIES. THANK YOU BOTH. MY NAME IS SHUMIN WANG PROGRAM DIRECTOR AT THE NATIONAL INSTITUTE OF BIOENGINEERING AND I'M GOING PRESENT NON-INVASIVE BRAIN FUNCTIONAL IMAGING TECHNOLOGY CONCEPT. BECAUSE IT'S IMPLEMENTATION MANAGED BY IBIB I HAVE ALSO PRESENTED A WEEK AGO AT A COUNCIL MEETING AND RECEIVED A HIGHLY VALUABLE COMMENTS. SO I'M GOING PRESENT THE CONCEPT HERE AGAIN TODAY AND BRING UP THOSE COMMENTS DURING MY PRESENTATION AND THEN WELCOME DISCUSSION ON THOSE POINTS. FIRST OF ALL, I WANT TO GIVE A BIG SHOUT OUT TO OUR TASK FORCE MEMBERS WHO COME FROM DIFFERENT PARTICIPATING I.C.s OF THE INITIATIVE. WE HAVE MULTIPLE MEETINGS AND PRESENTED THIS CONCEPT AT DIFFERENT LEVELS WITHIN NIH. THIS IS TRULY A TEAM WORK. SO THIS CONCEPT IS SUPPOSED TO MAKE A CONTRIBUTION TO THE FOLLOWING THREE PRIORITY AREAS IN THE BRAIN 2025 REPORT. AREA TWO MATCH WORKFORCE SKILLS FOR DIAGRAMS INTRODUCE FROM SYNAPSIS TO THE WHOLE BRAIN. FOR IMAGING WE ARE PRIMARY INTERESTED IN MICROSCOPY RESOLUTION AND MESO SCALE DOWN TO 100 MICRONS AND HOPEFULLY DURING THE SECOND PHASE OF OUR INITIATIVE WE CAN MAKE A SPATIAL SKILL AND THE BRAIN ACTION STO PRODUCE THE DYNAMIC PICTURE OF THE FUNCTIONING BRAIN BY DEVELOPING AND APPLYING METHOD FOR LARGE-SCALE MONITORING OF NEURAL ACTIVITY AND TALKING ABOUT DYNAMIC RANGE SPANS THREE OTHER MAGNITUDES TO HUMAN DYNAMICS AND ALL THE WAY TO A TENTHS OF A SECOND FOR MOLECULAR IMAGING SO THE THREE OTHER FOR THE RANGE IS ALSO HUGE. FINALLY THE PRIORITY AREA NUMBER 6 IS THE HUMAN NEUROSCIENCE TO DEVELOP METHODOLOGIES FOR HEALTHY HUMAN SUBJECT. IN 2019 THE BRAIN INITIATIVE ORGANIZED A WORKING GROUP 2.0 TO EVALUATE THE FIRST PHASE OF OUR INITIATIVE AND ALSO MADE SOME RECOMMENDATIONS FOR THE NEXT PHASE. HERE ARE SOME EXAMPLES RELATED TO NON-INVASIVE IMAGING. THE NUMBER 3 IN PRIORITY AREA 2 IS TO DEVELOP HIGH RESOLUTION FMRI WITH THE RESOLUTION AND CONSIDERED CURRENTLY THE BEST AS WE SPEAK. THE RESOLUTION OF FMR IS 0.01 CUBIC MILLIMETER SO IT REPRESENTS ORDER OF MAGNITUDE WITH IMPROVEMENT WHICH IS HUGE. SHORT TERM GOAL NUMBER 4 IN AREA 3 IS TO DEVELOP TOOLS FOR REALISTIC BEHAVIOR AND THINKING OF PEOPLE WALKING ON THE STREET OR TALKING TO EACH OTHER. CONVENTIONAL TECHNOLOGIES SUCH AS MRI OR PET ARE DESIGNED FOR IMAGING STATIONARY SUBSET OF PATIENTS. WE THOUGHT IT IT'S IMAGINABLE TO SOMEONE WALKING FREELY MOVING FREELY AND AS YOU CAN SEE THE CHALLENGE IS HUGE. THE QUESTION IS CAN WE ACTUALLY ACHIEVE THOSE GOALS. THIS CONCEPT HAS SOME PRECEDING ONES. WE HAVE RO1 PROOF OF CONCEPT RFA AND ALSO A U1 DURING THE FIRST PHASE OF THE BRAIN INITIATIVE. IN ORDER TO EVALUATE WHERE WE ARE NOW AND WHERE WE CAN GO IN 10 YEARS WE HAD A WORKSHOP AND THE FIRST WAS A DISSEMINATION WORKSHOP IN FEBRUARY FOCUSSING ON EVALUATING THE SUCCESS AND INVESTMENT THE BRAIN INITIATIVE MADE TO NON-INVASIVE TECHNOLOGIES DURING THE FIRST PHASE. THE SECOND IS A TRANSFORMATIVE WORKSHOP WHICH FOCUSES ON POSSIBLE NEW TECHNOLOGIES THAT COULD BE DEVELOPED IN THE NEXT FIVE TO 10 YEARS AND SOLICITED PUBLIC INPUT BASED ON THE OUTCOMES OF THE TWO WORK SHOPS AND RFI HERE. FIRST OF ALL, ACCOMPANYING NEW MODALITIES TO BROADEN THE APPLICABILITY AND THIS IS CURRENTLY BEING INVOLVED BY A RESEARCH GROUP WOULD ENABLE TAKING CORTICO HUMAN DYNAMICS INFORMATION FROM SUBJECT MOVING FREELY IN A LAB OR ON THE STREET OR TALKING TO ANOTHER PERSON. SO THIS CAPABILITY CANNOT EXIST PRIOR TO THE BRAIN INITIATIVE. FOR EXISTING MODALITIES SUCH AS MEG, PET AND F MRI WE ASSIST THE TECHNOLOGY AS YOU CAN SEE FROM THE LOWER LEFT CORNER THIS IS A HIGH RADIO FREQUENCY RECEIVER TO ENABLE THE PRECISION OF 400 MICRON LEVEL SO IMPROVEMENT IS POSSIBLE IN THE NEXT YEAR OR TWO. SO MOST THE PROJECTS MOVES TO THIS YEAR AND WE DO EXPECT TO DELIVER PRODUCT. SO BECAUSE OF THIS MUCH IMPROVED SENSITIVITY, WE COULD GET MUCH BETTER RESOLUTION DOWN TO THE MESO SCALE LEVEL BY USING THESE DEVICES WHICH WOULD NOT BE DONE PRIOR TO THE BRAIN INITIATIVE. DESPITE THE ACHIEVEMENT WE'RE NOT NEAR THE END OF THE ROPE. WE HAVE OPPORTUNITIES THAT EXIST AND LIST ON THE NEXT SLIDE. HERE'S ALTERNATIVES WE SUMMARIZED I WANT TO EMPHASIZE THE TOP TWO. THE FIRST ONE IS KNOX INTEGRATIVE SYSTEM TO ASSESS MULTIPLE SCALES TALKING ABOUT MESO SCALE TO MACRO SKILL. AND THE ASPECT OF BRAIN FUNCTIONAL CONNECTIVITY SO USING INDIVIDUAL MODALITIES WITH DYNAMICS AND MOLECULAR IMAGING HAS SEEN IMPROVEMENT AND THE INTEGRATED SYSTEM CAN PROVIDE A COMPLETE AND COMPLIMENTARY PICTURE OF ACTIVITIES STILL LACKING. WE RECOGNIZE THIS IS A GREAT OPPORTUNITY ESPECIALLY FOR DEVELOPMENT AND GONE TO A SPECIAL EMPHASIS. THE SECOND BULLET IS ON MACHINE LEARNING AND THE TECHNIQUES. BOTH ARE COMPLETION BASED. THIS IS SORT OF INDEPENDENT FROM HARDWARE DEVELOPMENT. SO WE HAVE A GREAT EXAMPLES IN THE PORTFOLIO THAT DEMONSTRATE SUCH MEASURES CAN IMPROVE THE PERFORMANCE OF VERY COSTLY EFFECTIVE MANNER. FOR INSTANCE, ONE OF THE AWARDEE DEVELOPED THE DATA-DRIVEN TECHNOLOGY AND APPLIED IT TO PROCESS HUMAN CONNECTOME PROJECT DATA. AND HE WAS ABLE TO IMPROVE SPATIAL RESOLUTION FOR DIFFUSION IMAGING FROM 1.5 METER CUBIC TO 0.375 METER CUBIC REPRESENTING THE SENSITIVITY IMPROVEMENT WITHOUT RE-WRITING THE ENTIRE EXPERIMENT. WE BELIEVE BY EMPHASIZING THIS COMPETITION-BASED TECHNOLOGY THIS COST-EFFECTIVENESS COULD PROPAGATE VERY SOON TO OTHER AREAS OF NON-INVASIVE IMAGING AND MAKE A BIGGER IMPACT TO THE COMMUNITY. SO ENCOURAGED BY THE NEW OPPORTUNITIES WE PROPOSED THE CONCEPT. THE CONCEPT IS THREEFOLD. FIRST IS TO CONTINUE THE MOMENTUM WITH THE INTEGRATIVE APPROACH FOR BRIDGING THE GAP BETWEEN MULTIPLE SKILLS AND ASPECTS. THIS IS CORRESPONDING TO THE FIRST BULLET IN THE PREVIOUS SLIDE. THE SECOND IS TO GUIDE FURTHER DEVELOPMENT BY EMPHASIZING TECHNOLOGIES SUGGESTED AT A WORKSHOP INSTEAD OF LETTING INVESTIGATORS IN THE FIELD. THE FIRST IS TO ENCOURAGE OUT OF THE BOX THINKING. WE DO BELIEVE THE TECHNOLOGIES CANNOT BE CONCEIVED BY CONVENTIONAL WISDOM MAY MAKE A HUGE IMPACT IN THE FIELD. HOWEVER, WE REALLY DON'T KNOW WHAT THE TECHNOLOGIES ARE AS A RESULT WE WANT TO ENCOURAGE SUCH THINK. THAT IS OUR GOAL. WHAT IS OUR STRATEGY TO ACHIEVE THAT? WE BELIEVE IT'S A PHASED AWARD MECHANISM IS THE BEST TO PROMOTE INNOVATION WHILE REDUCING THE RISK. BECAUSE SOME OF THE TECHNOLOGY OCCURRED HERE OF HIGH RISK. WE DO NEED TO FIGURE OUT THE FEASIBILITY BEFORE THE CONCEPT CANNOT BE FOR HUMAN IMAGING WITHOUT RISKING TOO MUCH MONEY ON THAT. THIS IS THE GENERAL STRATEGY. HERE IS AN EXAMPLE OF HOW WE CAN IMPLEMENT IT. I SHOULD MENTION WE'RE TALKING ABOUT CONCEPT HERE AND CAN HAVE DIFFERENT APPROACHES. I THINK WE THINK THIS IS A GOOD EXAMPLE. DOESN'T MEAN THIS IS THE ONLY EXAMPLE. SO DURING THE PHASE 1, WE WILL ALLOW UP TO THREE YEARS OF THE BUDGET TO LET THE INVESTIGATOR PROVE THE FEASIBILITY OF NEW CONCEPT. HERE'S THE TECHNOLOGY FEASIBILITY WHETHER YOU CAN VIEW IT OR NOT AND ALSO IS THE PROJECT FEASIBILITY. THAT MEANS YOU WANT TO BUILD IT WITHIN THE GIVEN TIME FRAME AND WHAT IS THE SCOPE OF THE PROJECT. AFTER FIGURING OUT THE FEASIBILITY OF THE TECHNOLOGY OR PROJECT, THE PROJECT CAN GO TO THE SECOND PHASE WHICH GIVEN MORE TIME AND BUDGET TO FULLY DEVELOP THE FUNCTIONAL PROTOTYPE WITH FIRST IN HUMAN IMAGING RESULT AND THIS IS WHERE WE RECEIVED SOME COMMENTS. SOME MEMBERS SUGGEST GIVEN THE FIVE YEAR GRANT SO FOR TRULY INNOVATIVE IDEA FOR OUT OF THE BOX THINKERS IS PROBABLY TOO SHORT TO DEVELOP THE CONCEPT ALL THE WAY TO FIRST IN HUMAN IMAGING. WE THINK THIS IS POSSIBLE DEPENDING ON THE NATURE OF THE TECHNOLOGY AND THE STARTING POINT, FOR INSTANCE, FOR SOME AGENTS MAY TAKE FIVE OR 10 YEARS TO DEVELOP A CONCEPT FOR A FIRST IN HUMAN SUBJECT. ON THE OTHER HAND, WE SHOULD KEEP A SIGNIFICANT CONCEPT IN MIND IF YOU ALLOW INVESTIGATOR TO STOP SHORT OF HUMAN IMAGING PROBABLY WOULD HURT THE SIGNIFICANCE OF THE PROJECT. SOMEWHERE IN THE MIDDLE IS PROBABLY PROBABLY IS BETTER AND WE WELCOME INPUT IN THE DISCUSSION SESSION. SO THE TASK FORCE ALSO CHALLENGED OURSELVES WITH THE QUESTION, CAN WE DO IT BETTER? LOOKING AROUND THE BRAIN INITIATIVE THERE'S MANY EXAMPLES OF TEAM-BASED SCIENCE. FOR EXAMPLE, THE BRAIN INITIATIVE CELLS CONSORTIUM AND THE BRAIN INITIATIVE CELL CENSUS NETWORK THE BICCN WHICH JOHN HAS PRESENTED A MOMENT AGO. THIS CONSORTIUM COORDINATED PROJECTS AND THERE WAS A PUBLISHING OF PAPERS IN THE PRIMARY MOTOR CORTEX ACROSS DIFFERENT SPECIES INTO 14 CATEGORIES AND MORE THAN 100 TYPES. SO LOOKING BACK INTO OUR NON-INVASIVE TECHNOLOGY DEVELOPMENT, THIS KIND OF TEAM-BASED SCIENCE IS REALLY LACKING ESPECIALLY IF YOU WANT TO ENCOURAGE THE DEVELOPMENT OF A HIGHLY-INTERGREAT GRATED SYSTEM AND WE NEED TO ENCOURAGE THE CROSS-TALK BETWEEN DIFFERENT DEVELOPERS. AS A RESULT WE THINK A CONSORTIUM WILL BE MUCH NEEDED IN THE NEXT PHASE OF THE BRAIN INITIATIVE JUST COMPROMISED OF STIMULATION OF THE RESEARCH IDEAS AND WE WOULD ORGANIZE MULTIPLE ANNUAL MEETINGS ON TOPICS OF BRAIN IMAGING, ASK AN INVESTIGATOR TO PRESENT THEIR PROJECT PROGRESS AND FUND THE NEURO TECHNOLOGY DEVELOPMENT TO PARTICIPATE. WE ALSO PLAN TO FORM AN AD HOC SUBGROUP ON ISSUES OF CONCERNS ACROSS THE CONSORTIUM AS TWO WORK SHOPS AND A BIG CONCERN IS THE PRACTICE AND STANDARDIZE THE DATA FORMAT TO ALLOW OTHER GROUPS TO ANALYZE THE DATA ACQUIRED BY SOME AWARDEES. THAT'S VERY IMPORTANT AND THE FUNCTIONAL MR COMMUNITY TO IMPROVE THE EFFECT SIZE OF SOME STUDIES AND THIS KIND OF CROSS-SITE ISSUES WILL BE DISCUSSED BY THE AD HOC GROUPS AND WE THINK BY USING THIS MAXIM WE CAT GET BETTER INNOVATIVE TECHNOLOGY MANAGEMENT AND WE'RE PUTTING IT TO THE FUNDING OPPORTUNITY ANNOUNCEMENT AND NOTICE OF WARD. AS A RESULT THE INVESTIGATORS FUNDED BY THE CONCEPT WILL BE REQUIRED TO PARTICIPATE THIS CONSORTIUM. NEXT SLIDE, PLEASE. THAT'S IT. I HOPE THIS GIVES YOU A PICTURE OF THIS CONCEPT AND I'LL OPEN THE FLOOR FOR FURTHER COMMENTS, DISCUSSION. >> THANK YOU, SHUMIN. WE TYPICALLY IS OUR MEMBERS TO DO A MORE IN DEP -- DEPTH LOOK AT THE CONCEPT AND START THE DISCUSSION. BRUCE. >> STARTING OUT WITH WHAT MAY NOT BE A GREAT SURPRISE OVERALL I'M VERY ENTHUSIASTIC ABOUT THIS IDEA. LOTS OF CLEAR THOUGHT HAS GONE INTO THE GROUP. I THINK SHUMIN AND HIS TEAM'S ARTICULATION OF WHEN THE PROGRESS MADE IS ON THE MARK BUT MOST IMPORTANT HIS CONCLUSION THERE'S SIGNIFICANT ADDITIONAL PROGRESS TO BE MADE I THINK IS LIES SUPPORTED BY WHERE WE ARE AND AREAS FLOATING IN THE COMMUNITY. SOME OF THE THEMES I THOUGHT WERE STRONG AND MIGHT EVEN BE HIGHLIGHTED WHEN AN ULTIMATE RFA MIGHT APPEAR, THE PUSH FROM MACRO SCALE TO MESO SCALE IS CERTAINLY ONE THAT SHUMIN HAS ALLUDED TO. I THINK WE'RE REALLY ON THE THRESHOLD NOW OF USING SOME OF OUR TOOLS AND CERTAINLY MR TODAY AND PROGRAMS IN THE FUTURE INTEGRATION OF OPTICS AND ACOUSTICS, FOR EXAMPLE, TO BE ABLE TO MEASURE BRAIN ACTIVITY AT DIFFERENT LEVELS AND ONE THESE THINGS WHERE EVEN RELATIVELY MODEST IMPROVEMENTS IN THE TECHNOLOGY CAN TAKE US TO THE POINT WHERE WE CAN RELIABLY DO THESE EXPERIMENTS ACROSS THE ENTIRE BRAIN WHICH I THINK WILL MAKE A PROFOUND IMPACT BECAUSE WE REALLY DON'T KNOW MUCH ABOUT HUMAN BRAIN MESO SCALE ARCHITECTURE AND FUNCTION AND YET I THINK WE'RE GAINING ON THE ABILITY TO DO THAT. IN A SIMILAR VEIN, THE TEMPORAL RESOLUTION TO USE THE TECHNIQUES ESPECIALLY THOSE MAYBE BASED ON HUMAN DYNAMICS IS FOR BEHAVIOR IN THE DELTA RANGE AND SLOW WAVES. IF WE CAN CONTINUE TO PUSH THROUGH ON THE SENSITIVITY ISSUES SHUMIN LAID OUT, I THINK THAT SHOULD ALLOW US TO LOOK AT WHOLE BRAIN INTEGRATION OF BEHAVIORS AT SOME FREQUENCIES AND THEN WITH THE INTEGRATION OF TECHNOLOGIES THE ELECTROPHYSIOLOGICAL TOOLS CERTAINLY PUSH TO A BROAD RANGE OF COHERENT FREQUENCIES WE CAN LOOK AT WHICH HIGHLIGHTS ANOTHER ELEMENT SHUMIN REINFORCED HERE WHICH IS THE NOTION OF ENCOURAGING THE INTEGRATION OF TECHNOLOGIES. CERTAINLY THERE'S BEEN LOTS OF PROGRESS IN THE PAST AND THINGS LIKE INTEGRATING MR AND PET BUT I THINK THE INTEGRATION OF OPTICS AND ACOUSTICS WE'VE SEEN GOOD PROGRESS BUT MORE TO BE DONE PUSHING THAT IN THE HUMAN REALM AND ACOUSTICS AND HUMAN PHYSIOLOGY AND WE'VE SEEN THE BEGINNINGS OF ACTIVITY BUT THESE DOMAINS ARE REALLY ONES THAT ARE RIPE FOR CREATIVE INPUT AND SIGNIFICANT INVESTMENTS TO PUSH THEM THROUGH AND HOLD GREAT PROMISE AT LEAST IN STUDYING THE CORTEX TO BE ABLE TO ROUTINE GET US TO SENSITIVITY AND SPATIAL AND TEMPORAL RESOLUTIONS AT THE MESO SCALE WE'RE LOOKING AT. I THINK ANOTHER OPPORTUNITY THAT WAS KIND OF ALLUDED TO AND SOMETHING WE CAN CONSIDER BEING MORE EXPLICIT ABOUT IS THE NEURAL CHEMICAL SIDE OF THINGS AND SHUMIN POINTED OUT THE INVESTMENT IN PET TECHNOLOGY REALLY OFFER ONE OF THESE ORDER OF MAGNITUDE IN IMPROVEMENT IN SENSITIVITY AND MAYBE WITH A.I. TOOLS MAYBE EVEN MORE THAN THAT. SOME SAY UPWARDS OF A FACTOR OF 100 IN SENSITIVITY. THAT'S A BIG DEAL. THAT THEN ALLOWS YOU TO IMAGINE, FOR EXAMPLE, STUDYING CHILDREN WITH NUCLEAR TECHNIQUES WHICH YOU WOULDN'T OTHERWISE CONSIDER UNDER CURRENT DOSE REGIMES BUT WHEN THEY'RE NO GREATER THAN WHAT YOU WOULD EXPECT FROM A MODERN AIRLINE FLIGHT NOW THE IRB MAY LOOK UPON THOSE DIFFERENTLY. AND I THINK THERE'S OPPORTUNITIES NATIONALLY TO NET EFFORTS IN DEVELOP THE NEUROCHEMICAL ARMAMENTARIAN WORK AND NOT SURE HOW IT WOULD FIT WITH THE RFA THERE BUT MAYBE THERE'S OPPORTUNITIES TO ENCOURAGE LINKAGE BETWEEN THE NEURAL CHEMICAL OPPORTUNITIES AND ALL THE GREAT WORK HAPPENING IN THE CELL CENSUS I THINK IS A GREAT OPPORTUNITY. ONE OF THE CHALLENGES I THINK WE'LL HAVE AS A FIELD, AND WE SAW THIS FROM THE VERY FIRST ROUND, I REMEMBER THE FIRST RFAs WHICH WERE PRETTY EXPLICIT IN LOOKING FOR OUT OF THE BOX IDEAS. IN FACT THERE WAS EVEN LANGUAGE WRITTEN IN IT SHOULDN'T BE CONVENTIONAL THINGS BUT WE HAVE RETURN ON INVESTMENT IN BIG MAGNETS. THAT'S WHAT THE STUDY SECTION WENT FOR. SO I THINK ONE OF THE REAL CHALLENGES WE HAVE IN THIS IS OUT OF THE BOX THINKING IS NOT LIES ACCOMMODATED BY A CONVENTIONAL STUDY SECTION DYNAMICS. SO THAT'S A CHALLENGE I KNOW YOU FOLKS UNDERSTAND BUT ESPECIALLY IMPORTANT WHEN YOU REALLY WANT TO PUSH IDEAS THAT DON'T HAVE A LOT OF PRELIMINARY DATA AND PEOPLE AREN'T FAMILIAR WITH BUT ALMOST BY DEFINITION THERE'S NOT GOING TO BE A ROOM OF PEOPLE WHO UNDERSTAND THE TECHNOLOGY AND DEVELOPMENT BECAUSE IF IT WERE IT WOULDN'T BE OUT OF THE BOX ANYMORE. HOW TO GET THOSE IDEAS THROUGH STUDY SECTIONS WILL HAVE TO DEPEND ON HOW THE RFA'S WRITTEN AND SOMETHING TO THE DEGREE OF HOW WE ORGANIZE THOSE GROUPS. THE CONSORTIUM IS A GREAT IDEA. ONE THING I MIGHT ADD TO THAT AND THE NIH TALKS ABOUT DATA SHARING AS ROUTINE. I THINK THIS IS A DOMAIN WHERE CONCERTED EFFORTS AROUND INCLUDING EXPLICIT PLANS AROUND DATA SHARING AND RESOURCES THAT PEOPLE NEED TO UNDERSTAND THEY HAVE TO RESOURCE DATA SHARING. THEY CAN'T JUST SAY THEY'RE GOING SHARE IT. IT TAKES EFFORT AND MONEY TO MAKE THAT HAPPEN. I WOULD AT LEAST ENCOURAGE THAT TO BE SOMETHING EXPLICIT EVALUATION CRITERIA AND MAKE IT CLEAR WE EXPECT THAT IT DOESN'T COME FOR FREE. THEN YOU TALKED ABOUT THE ISSUE OF TIMING AND A LOVE THE TWO-PHASED MECHANISM. IT MAKES SENSE BUT THE NOTION YOU WOULD WANT TO GET TO FIRST IN HUMAN USE IS GREAT BUT OF COURSE DOING THAT IN FIVE YEARS IS CHALLENGING AND IF GETTING TO HUMANS IN FIVE YEARS IS A REVIEW CRITERIA, THAT MAY DISCOURAGE SOME OF THE OUT OF THE BOX THINK YOU'D LIKE WHERE THOSE TIME FRAMES ARE LIKELY TO BE LONGER AND REVIEWERS MIGHT REALISTICALLY UNDERSTAND AND HOW TO BALANCE THOSE I LIKE THE FAZE PHASED APPROACH TO REJECT AREAS THAT AREN'T MAKE PROGRESS BUT TO MAKE SURE PROGRESS DON'T GET KILLED BECAUSE REVIEWERS PERCEIVE THE NEED TO GET IT INTO HUMANS IN THAT FIVE-YEAR TIME FRAME I FIND THAT AS TOO GREAT A HURDLE. WE WOULDN'T WANT TO REJECT THOSE IDEAS. I KNOW WE WOULDN'T WANT TO REJECT THE IDEAS AND SOMETHING I ENCOURAGE TO THINK ABOUT MORE AND PLENTY OF GREAT STUFF HERE AND LOTS OF GREAT OPPORTUNITIES TO BEGIN TO CONNECT WHAT WE'RE DOING FROM THE TOP DOWN TO WHAT OF COURSE IS HAPPENING AT THE CELL CENSUS AND ELECTROPHYSIOLOGICAL LEVEL FROM THE BOTTOM UP. >> THANK YOU SO MUCH, BRUCE, FOR YOUR SUPPORT AND GREAT COMMENTS. AS TO THE FIRST IN HUMAN TEST, IT'S TRULY ASPIRATIONAL IN A SENSE. ALSO BECAUSE IT GOES TO SUPPORT HUMAN NEUROSCIENCE. IT'S SORT OF DIFFICULT FOR US TO GO LOWER AND ON THE OTHER SIDE I CONSIDER YOUR COMMENTS ESPECIALLY WHETHER THE OUT OF THE BOX THINKERS CAN MAKE IT TO HUMAN IN FIVE YEARS. WE LOOK AT OUR PORTFOLIO AND THERE'S CHANGE TO LARGE ANIMALS IN FIVE YEARS AND DO NEED A TARGET OTHERWISE WE CAN PROPOSE SOMETHING WITH NO END RESULT. >> I WONDER IF THE TARGET WOULD BE RATHER THAN HAVING THE PROTOTYPE WORK IN HUMANS, BASICALLY EITHER THAT FOR HAVING DETAILED MODELLING AND PRELIMINARY DATA TO GO TO THE BRAIN AND GEOMETRY OF SKULL THICKNESS FOR HUMANS AND A WAY TO SHOW IT'S HUMAN CAPABLE EVEN IF YOU HAVEN'T DONE ALL THE ENGINEERING TO GET TO THAT POINT BECAUSE I AGREE WITH YOU, IT SHOULD BE DEVOTED TO WHAT IT TAKES TO IMAGE THE BRAINS OF HUMANS. THAT MAY BE ANOTHER WAY TO PHRASE THINGS EITHER DEMONSTRATION OR CLEAR DEMONSTRATION BASED ON MODELLING AND DATA AND LARGE ANIMALS IT WILL BE FEASIBLE TO MOVE TO HUMANS. THAT MAY BE ANOTHER WAY TO CUT IT. AND THAT SHOULD BE DOABLE IN FIVE YEARS, I AGREE. >> BRUCE, THAT'S A GREAT POINT. WHAT WE WANT IS A CLEAR PATH NOT JUST A PROMISE. THANK YOU. SUSAN, SHOULD WE MOVE TO THE NEXT DISCUSSANTS AND THEN CIRCLE BACK FOR GENERAL DISCUSSION? THANK YOU, BRUCE. >> SURE. BRUCE, YOU SAID SO MUCH AND I'LL TRY TO HIGHLIGHT IT. IT WAS FANTASTIC. I'M HUGELY SUPPORTIVE BECAUSE IT WILL BE A HUGE IMPACT IN CIRCUIT DIAGRAMS AND ACTIVITY IN THE DYNAMIC RANGE AND TO THINK ABOUT SPATIAL AND TEMPORAL CONSIDERATIONS AS WE SCALE UP TO HUMAN TO THINK ABOUT CIRCUITS OF BEHAVIOR AND ALSO CIRCUIT DISORDERS IS OF PROFOUND IMPORTANCE AND AT THE POINT WE SHOULD ASPIRE TO DO THAT WITH OTHER AREAS GETTING ATTENTION IN THE BRAIN AND USING A USE CASE IS IMPORTANT WHY NOT GAIN SOMETHING ABOUT A BEHAVIOR OR EVEN A DISORDER. I WOULD SUGGEST THAT WE THINK HARD ABOUT WHAT WE WOULD CHARACTERIZE AS AN IMPORTANT USE CASE AS WE MOVE THROUGH THIS DEVELOPMENT, THIS SPECTRUM IS WHERE THE PROCESS OF DEVELOPING. AND MANY DISORDERS COULD VERY BE VERY ADAPTABLE TO A KNOWN LESION IN A CONNECTION PATHWAY THAT COULD MAKE IT VERY GOOD PROOF OF PRINCIPLE FOR YOU. I ALSO GIVEN I'M REPRESENTING NICHD AS WELL AND ACROSS THE LIFE SPAN, I THINK WE HAVE TO CONSIDER HOW WE'RE GOING THINK ABOUT DEVELOPING BRAIN VERSUS AGE BRAIN. THERE'S ANOTHER DYNAMIC RANGE THERE IN THE SAME BRAIN AND WHAT DOES HOW ARE WE GOING THINK ABOUT THAT MAYBE AT THE ANIMAL LEVEL BUT STILL AS WE SCALE TO THE HUMAN, WHAT DO WE HAVE TO CONSIDER IN A DEGENERATING BRAIN VERSUS A DEVELOPING BRAIN WHERE FROM ONE WEEK TO THE NEXT IT'S QUITE DIFFERENT. SO TO REMEMBER THAT. I THINK THAT I WANTED TO PICK UP ON SOMETHING SAID EARLIER WHERE TED ABEL WAS TALKING ABOUT BEING BRAIN/NERVOUS SYSTEM CENTRIC. AS WE THINK OUT SIDE THE BOX CAN WE THINK CONNECTING THE ENTERIC NERVOUS SYSTEM AND THE TERRIFIC RAL SYSTEM AND I THINK WE'RE READY TO DO IT AT SOME LEVEL MAYBE NOT IN THE HUMAN BUT MAYBE IN SOME EXPERIMENTAL MAN MODELS. THAT WOULD BE AN INTERESTING PIECE TO CONSIDER. I THINK FOR TAKING IT TO THE NEXT LEVEL, INTO THE PHASE 1-2 ADMINISTRATIONS I AGREE CONSORTIUM ARE KEY. WE HAVE TO THINK ABOUT U MECHANISMS OUTSIDE THE R01 AND THINK OF GO/NO-GO EXAMPLES LIKE THE SHARK TANK APPROACH USED BY THE IMAGE INSTITUTE AND ANTICIPATING HOW WOULD YOU MAKE THOSE CHOICES AND HOW WOULD YOU SET THAT UP SO IT'S JUSTIFIED. DON'T FORGET TO EXPLICITLY THINK OF HOW WE'LL REACH OUT TO THE NON-NEURAL SCIENTISTS THE ENGINEERS AND THE A.I. AND HOW TO BUILD THAT BECAUSE OF COURSE IT'S GOING TO BE KEY. THE OTHER THING IS I THINK THE PHASE 2,IT'S HARD TO SAY FIVE YEARS. I THINK THAT MAY NEED TO BE QUALIFIED OR REMOVED AT THIS POINT BECAUSE IT COULD CONSTRAIN PEOPLE TO THINK SMALL BECAUSE THEY HAVE TO GET SOME PLACE IN FIVE YEARS AND IF YOU'RE TRYING TO GO BIG AND GO OUTSIDE THE BOX YOU MIGHT NOT. THEN FINALLY, I THOUGHT THAT YOU MIGHT WANT TO ALSO THINK ABOUT HOW WE'LL USE NEURO ETHICS TEAM HAVING HEARD FROM DR. GREELY EARLIER. THIS IS KEY BECAUSE YOU MAY BE UNCOVERING SOME -- AS YOU MOVE INTO THE HUMANS YOU MAY HAVE THINGS THAT TO BE SHARED OR MANAGED LIKE WE CAN ALL THESE OTHER KINDS OF EXPERIMENTAL PARADIGMS. SO I THINK I'LL STOP THERE. THOSE ARE MY THOUGHTS TO ADD TO THE AMAZING SUMMARY THAT BRUCE GAVE. >> THANK YOU SO MUCH, FRANCES. >> TODD, DID WANT TO COMMENT AND THEN WE CAN HAVE A MORE GENERAL DISCUSSION? >> SURE, BRUCE AND FRANCES BOTH SAID MANY OF THE COMMENTS I WOULD GOING TO SAY SO THANK YOU FOR DOING ALL THAT WORK. I'LL JUST ECHO A FEW OF THE ONES I REALLY THINK ARE CRITICAL. THE NEUROETHICS ONE TO FINISH WHERE FRANCES LEFT OFF TO ME IS SOMETHING THAT DID AND FROM HANK'S SUMMARY OF THE NEWG, THIS IS PARTICULARLY A PLACE WHEN WE'RE TALKING ABOUT NEW NONINVASIVE HUMANS AND THE NEURO ETHICS ISSUES AND WHO WITH BENEFIT AND YOU CAN IMAGINE BUILDING IN SOMETHING LIKE THE PARALLEL TO THE PDP WHERE YOU'RE GOING TO HAVE A COMPONENT WHERE YOU SAY, LIKE WHAT ARE THE ETHICAL ISSUES THE NEURAL ETHICS ISSUES YOU CAN ANTICIPATE. HAVE YOU TALKED TO CONSULTANTS ON THIS AND IT SEEMS LIKE IN THIS TYPE OF DESIGN AND OF PROGRAM THAT CAN BE SOMETHING THAT MAY BE PARTICULARLY IMPORTANT. IN TERMS OF WHERE THE TECHNOLOGIES ARE GOING, OBVIOUSLY THESE ARE GOING TO BE CRITICAL. I DO SUPPORT AND THIS IS A FANTASTIC IDEA AND I'M VERY SUPPORTIVE OF IT. THE NEURAL CHEMICAL, I WANT TO ECHO BRUCE'S IDEA AND FRANCES, THINKING ABOUT CONNECTIONS BETWEEN BRAIN AND OTHER BODILY SYSTEMS ARE GOING TO BE REALLY IMPORTANT COMING FROM NCCIH AND ONE OF THE THINGS EMPHASIZED IS THE WHOLE PERSON APPROACHES. SO THINKING ABOUT KANG WE THINK OF THE CONNECTIONS BETWEEN THINGS LIKE THE BRAIN AND HORMONAL SYSTEM AND THINK ABOUT THE MUSCLES. ARE THERE GOING TO BE SUPPORT FOR TECHNOLOGY ENCOURAGING THOSE KINDS OF TECHNOLOGIES AND THAT MAY BE AT A VERY EARLY STAGE AND THINKING BEYOND THE CNS SEEMS LIKE AN IMPORTANT DIRECTION. A QUESTION I HAD I WOULD LIKE TO HEAR MORE ABOUT, IT SEEMED THERE WAYS SLIGHT DISCONNECT BETWEEN THE TECHNOLOGY AND METHODOLOGY FOCUSSED APPROACHES FROM THE ONES THAT ARE MORE ANALYTIC OR SOFTWARE THAT MACHINE LEARNING AND A.I. IN TERMS OF THAT IF YOU HAD A PROJECT HOW IT WILL BE PRIMARILY ON THAT DIRECTION WILL NOT FIT IN WITH THIS PHASED APPROACH AS WELL BECAUSE THE USED CASE EXAMPLE YOU GAVE USING MACHINE LEARNING ARE MODEL BASED AND NEED NETWORKS TO IMPROVE RESOLUTION FROM AS A SECONDARY DATA ANALYSIS OF HUP. IS THAT GOING TO FIT INTO THIS AND HOW ARE YOU GOING TO ENCOURAGE OR WILL THAT BE A PIECE OR TECHNOLOGY AND SOFTWARE ANALYTICS PART THAT WILL BE INTEGRATED OR CAN PEOPLE HAVE PROJECTS THEY ARE PROPOSING THAT WILL BE FULLY NON-HARDWARE TYPES OF PROJECT AND HOW WILL THAT FIT IN WITH THIS AGREEMENT? THAT'S SOMETHING I WAS THINKING ABOUT AND WANT TO ECHO THE IDEA OF THINKING CAREFULLY ABOUT THESE GO/NO-GO MILESTONES AND BEING CREATIVE ABOUT THAT I THINK IT WILL BE IMPORTANT BECAUSE HOW YOU GET FROM THE DECISION OF THE PHASE 1 TO PHASE 2 AND THE CRITERIA USED IN MAKING THE CLEAR TO THE INVESTIGATORS IS ALSO USEFUL. FINALLY, THESE TEAMS. I LOVE THIS IDEA OF THE CONSORTIUM. ECHOING AGAIN, THE IDEA OF PEOPLE THINKING ABOUT THE CASE OF THESE AND HOW THEY MET ON THE TEAM THAT YOU'RE THINKING ABOUT WHAT ARE THESE TECHNOLOGIES GEARED FOR IN TERMS OF THE KEY NEUROSCIENCE THEORETICAL QUESTIONS THEY'LL BE AIMED AT I THINK WILL BE VERY IMPORTANT AS WELL AND TO HAVE THAT CONSORTIUM TO FACILITATE. JUST WANT TO ECHO THIS IS GREAT AND SUPPORTIVE OF IT AND THANK YOU FOR BRINGING IT TO US. I'LL STOP THERE. >> THANK YOU, SO MUCH, TODD FOR YOUR COMMENTS. >> WE HAD A COMMENT IN THE CHAT. WOULD YOU MIND IN MUTING YOURSELF AND ASKING OR MAKING THE SUGGESTION SO VIDEOCAST PEOPLE CAN HEAR IT AS WELL? >> YEAH, THE THOUGHT WAS A LOT OF TIMES DWOE REQUEST OR TRY TO GET INTO HUMAN WITHIN FIVE YEARS OF A PROGRAM AND IT IS AGGRESSIVE WITHOUT QUESTION BUT SOMETIMES FIT LOOKS LIKE AS WE GET -- IF IT LOOKS AS WE GET IN THE PROGRAM TWO OR THREE YEARS IN IT MAY NOT BE POSSIBLE, WE THEN TRY TO ASK, CAN WE AT LEAST GET INTO THE FDA WITH THE PRE-SUB SO WE HAVE A LOT OF THE SAFETY AND EFFICACIES STUDIES DONE AND MAYBE NOT IN HUMAN YET BUT A HUGE STEP FORWARD RATHER THAN JUST DOING ANIMAL STUDIES AND THE GRANT ENDS WITHOUT HAVING GOT TO THE FDA AT ALL. AND WHAT WE LEARNED IS HELPFUL IS INFORMATIONAL MEETINGS WITH THE FDA BEFORE PRE-SUBS BUT A TIME FOR THE P.I. TO DISCUSS WHAT THE PROGRAM IS AND THE TYPE OF TECHNOLOGIES TO BE DEVELOPED. SOME OF THAT STUFF THE FDA MAY NOT HAVE HEARD OF OR BE READY FOR YET SO HAVING AN EARLY INDICATOR AS TO WHERE THE RESEARCH MAY GO UNDER THE GRANT CAN BE REALLY HELPFUL. I WANTED TO SHARE THAT AND HAS WORKED ALL WET ON THE DARPA SIDE. >> THANK YOU SO MUCH. >> TED, DOW DID YOU HAVE A COMMENT OR QUESTION? >> YES, HI. THIS IS VERY INTERESTING. I WANTED TO ECHO THE COMMENTS ON NEURO CHEMISTRY AND DEVELOPMENT. THEY'RE BOTH IMPORTANT ISSUES TO HIGHLIGHT AND SOMETHING THAT'S NOT JUST FROM NINDS BUT DIRECTOR AND NEURO CHEMICALLY IT'S INTERESTING HOW MUCH PHYTO PHOTOMETRY HAVE INFLUENCED AND I THINK IT'S IMPORTANT. I ALSO WANTED TO COMMENT ON THE FIVE-YEAR DELIVERY THINGS. OTHER ORGANIZATIONS DO THIS QUITE DIFFERENTLY WHERE DARPA, FOR EXAMPLE, WOULD START WITH A GROUP OF INVESTIGATORS AT THE BEGINNING AND MAYBE END WITH ONLY ONE OR TWO OF THEM NOT ALL SIX OR SEVEN. NIH DOESN'T EXACTLY WANT TO DO THAT BUT THEY'RE OBVIOUSLY MORE FOCUSSED ON OUTCOME AND YOU GET KICKED OFF THE ISLAND IF YOU'RE NOT DOING THE THING. THERE'S MORE AGGRESSIVE WAYS TO MAKE A DELIVERY HERE IF THAT'S WHAT YOU'RE TRYING TO DO. LASTLY, I WANT TO MAKE A GENERAL POINT I MADE WITH THE ORIGINAL CONNECTOME PROJECT DECADE AGO OR 15 YEARS AGO AND THAT IS A FUNDAMENTAL HALLMARK OF THE INFORMATION SYSTEM IS IT'S PLASTICITY. IT WILL DRIVE OUR ABILITY TO RESPOND TO EXPERIENCE AND REMEMBER EXPERIENCE AND WHAT DRIVES A LOT OF DISEASE AND COMPENSATION BECAUSE OF THAT PLASTICITY CAN HELP PEOPLE FUNCTION BUT CAN ALSO MAKE THEM WORSE OR WORSE IN DIFFERENT WAYS. SO I JUST WANT TO UNDER SCORE HOW MUCH PLASTICITY IS INVOLVED IN THESE THINGS. IT'S ONE THING TO KNOW HOW THESE THINGS ARE CONNECTED BUT IF WE GO TO SLEEP AND WAKE UP AGAIN, THEY'LL CHANGE. AND I REMEMBER COMMENTING ON A MICROSCALE AT HARVARD WHERE THEY WERE COUNTING SYNAPSES WITH EVERY BIOLOGY MAJOR WAS COUNTING SYNAPSES IN THE MOUSE CORTEX AND IF THE MOUSE FELL ASLEEP OR CHANGED IT WOULD HAVE CHANGED AND THINKING ABOUT PLASTICITY IS AN IMPORTANT CONCEPT AND WE MAY KNOW HOW IT CHANGES AND THAT IS VERY IMPORTANT. TO ME WE LOSE TRACK OF THAT PLASTICITY AND DO IN THE GENETIC BASIS OF BRAIN DISORDERS BECAUSE WE DON'T THINK HOW THAT'S READ OUT, WE THINK OF WHAT IT IS. THAT'S A SOAPBOX OF MINE I THOUGHT I WOULD JUMP ON. I HOPE THAT'S OKAY. >> THANK YOU SO MUCH FOR YOUR COMMENTS, TED. >> FRANCES. >> THE ISSUE OF PLASTICITY I REMEMBER I CAME OUT WHEN JOHN AND I HAD OUR ONE-ON-ONE CALL. THERE'S NO OTHER ORGAN SYSTEM WHERE THE CELLS ARE CHANGING BY THE MICROSECOND. WHAT IS AN INTERESTING THING TO CAPTURE, WHICH I DIDN'T MENTION THIS, TRYING TO MAP AT WHAT LEVEL AT CONNECTIVITY MAP IS THERE A HIGH DEGREE OF CHANGE IN THE MILLISECOND VERSUS YEARS OR NONE. AND GETTING A SENSE OF THAT RANGE IS PROBABLY GOING TO BE DIFFERENT BETWEEN SPECIES AND CERTAINLY BETWEEN OUR BRAIN AREAS BUT COULD BE A FASCINATING OUTSIDE OF THE BOX ENDEAVOR TO THINK ABOUT IN SOME WAY FOR SOME GROUPS IN INTERPRETING HUMAN BEHAVIOR AND WHAT IS REVERSIBLE VERSUS WHAT IS NOT. >> THANK YOU SO MUCH. >> I'LL JUMP IN AND SAY THE COMMENT ABOUT PLASTICITY SAY GREAT COMMENT. I COMPLETELY AGREE AND REINFORCE THE BROAD DEFINITION OF WHAT WE'RE AFTER HERE WHEN WE TALK ABOUT BRAIN FUNCTION. THAT'S NOT A SINGULAR THING SO MAKING CLEAR WHEN WE USE THAT WE DON'T MEAN NECESSARILY FUNCTION IN THE WAY SAY SOMEBODY DOING THAT DOES BUT MAY PART OF IT BUT INCORPORATES ALL THE LINK ELEMENTS INCLUDING MEASUREMENTS OF PLASTICITY AND NEUROCHEMICAL CHANGES AND OVER THE TIMES OF RANGE OF TIME FRAMES FRANCES TALKED ABOUT ALL RELEVANT NOR FUNCTION OF THE BRAIN. WE WANT TO BE CLEAR THAT WE'RE USING WHAT I CAUGHT BIG F FUNCTIONAL IMAGING NOT LITTLE F FUNCTIONAL IMAGING. >> THERE'S ALREADY A RO1 OUT THERE ABOUT NEURO IMAGING RESEARCH AND PORTABLE MRIs ALREADY HAS A NEUROETHICS MORE INTERACTIONS WITH THE NEUROETHICS FOLKS AND THE NEWG AND THE NEURO ETHICS GROUP WOULD BE EXCITED ABOUT THE INTERACTIONS. >> WE DID ONE AND WE HAD A RECIPIENT OF THE SUPPLEMENTAL AWARD FROM THE UL1 GRANT AND STARTED A TOOL FOR THAT ONE. WE DO KEEP IN MIND AND WILL CONTINUE DOING THAT IN THE FUTURE. IT'S A VERY IMPORTANT TOPIC. >> -- ALSO TO THE NEURO CHEMICAL SIDE THERE'S ONGOING DISCUSSION ABOUT HOW TO SEPARATE THAT. IT'S A HUGE TOPIC AND PRELIMINARY FROM AN IMPLEMENTATION RESEARCH AND SAFETY AND THERE'S A HUGE DISCUSSION AND HOPE THERE'S NEW OPPORTUNITY IN THE FUTURE AND WITH OTHER PARTS IS A BIGGER CHALLENGE. NOW YOU WANT TO INVESTIGATE OUTSIDE THE BRAIN AND HAVEN'T DONE MUCH DEVELOPMENT IN THAT IMAGING. IT'S A NEW OPPORTUNITY AND BROADER AND LARGER SCALE AND TRULY EXCITING. >> I'M NOT SEEING ANY OTHER HANDS RAISED. CLEARLY A LOT OF ENTHUSIASM FOR THIS CONCEPT AND SOME ADDITIONAL THINGS TO THINK ABOUT. THANK YOU ALL. I'M GOING ASSUME THE GENERAL FEELING IS THIS IS A GOOD CONCEPT FOR BRAIN TO BE SUPPORTING AS WE MOVE FORWARD. ARE THERE ANY OBJECTIONS, SPEAK NOW? WELL, THANK YOU ALL VERY MUCH. AGAIN, THIS HAS BEEN A VERY RICH CONVERSATION AND I THINK ALL OF YOUR INPUT IS REALLY HELPFUL. ALSO, I WANTED TO REMIND PEOPLE THE NEUROETHICS WORKING GROUP MEETING FROM YESTERDAY WILL BE ON THE NIH VIDEOCAST SIDE AND ARCHIVED THERE SO FOR THOSE INTERESTED IN TRYING TO PUT IN ADDITIONAL IDEAS OF HOW THAT GROUP CAN MOVE FORWARD, THAT WILL BE AVAILABLE IF YOU MISSED IT YESTERDAY. >> I WANT TO THANK YOU ALL FOR YOUR GREAT COMMENTS. I WILL WRITE MY NOTES AND TAKE THEM INTO FULL CONSIDERATION AND IMPLEMENTATION. THANK YOU AGAIN. >> SO WE ARE READY FOR A BREAK FOR LUNCH BREAK OR SOME KIND OF BREAK. WE'LL BE RESUMING AT 2:30 AND THAT WILL BE THE CLOSED SESSION AND THAT WILL AGAIN BE WITH JUST THE COUNCIL MEMBERS AND FEDERAL EMPLOYEES. SO LOOK FORWARD TO TALKING TO YOU THEN AND THERE IS A SEPARATE ZOOM LINK TO GET ON TO THE CLOSED SESSION. >> THANK YOU ALL FOR YOUR GREAT COMMENTS. WE WILL DEFINITELY TAKE THESE UNDER CAREFUL CONSIDERATION AND FOR THE COUNCIL MEMBERS WORKING GROUP WE'LL SEE YOU IN HALF AN HOUR OR SO? MORE? 2:30. >> 40 MINUTES. >> GREAT. THANKS SO MUCH.